Sodium dodecyl sulfate#safety#Oral concerns

File:Sodium dodecyl sulfate.jpg for use in the laboratory]]

The critical micelle concentration (CMC) in water at 25 °C is 8.2 mM, and the aggregation number at this concentration is usually considered to be about 62.{{cite journal | last1 = Turro | first1 = N.J. | last2 = Yekta | first2 = A. | year = 1978 | title = Luminescent probes for detergent solutions. A simple procedure for determination of the mean aggregation number of micelles | journal = J. Am. Chem. Soc. | volume = 100 | issue = 18| pages = 5951–52 | doi=10.1021/ja00486a062 }} The micelle ionization fraction (α) is around 0.3 (or 30%).{{cite journal |author1=Bales, Barney L. |author2=Messina, Luis |author3=Vidal, Arwen |author4=Peric, Miroslav |author5=Nascimento, Otaciro Rangel | title = Precision Relative Aggregation Number Determinations of SDS Micelles Using a Spin Probe. A Model of Micelle Surface Hydration | journal = J. Phys. Chem. B | year = 1998 | volume = 102 | issue = 50 | pages = 10347–58 | doi = 10.1021/jp983364a}}

SDS is mainly used in detergents for laundry with many cleaning applications.Smulders, Eduard ; Rybinski, Wolfgang; Sung, Eric; Rähse, Wilfried; Steber, Josef; Wiebel, Frederike & Nordskog, Anette. (2002) "Laundry Detergents," in Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-VCH, {{doi|10.1002/14356007.a08_315.pub2}}{{page needed|date=March 2016}} It is a highly effective surfactant and is used in any task requiring the removal of oily stains and residues. For example, it is found in higher concentrations with industrial products including engine degreasers, floor cleaners, and car exterior cleaners.{{CN|date=April 2022}}

It is a component in hand soap, toothpastes, shampoos, shaving creams, and bubble bath formulations, for its ability to create a foam (lather), for its surfactant properties, and in part for its thickening effect.{{cite web|url=https://hpd.nlm.nih.gov/cgi-bin/household/brands?tbl=chem&id=78|title=Household Products Database – Health and Safety Information on Household Products|work=nih.gov|access-date=13 March 2016|archive-date=12 June 2018|archive-url=https://web.archive.org/web/20180612113209/https://hpd.nlm.nih.gov/cgi-bin/household/brands?tbl=chem&id=78|url-status=dead}}

Sodium dodecyl sulfate, appearing as its synonym sodium lauryl sulfate (SLS), is considered a generally recognized as safe (GRAS) ingredient for food use according to the USFDA (21 CFR 172.822).{{cite web|url=http://www.gpo.gov/fdsys/granule/CFR-2013-title21-vol3/CFR-2013-title21-vol3-sec172-822|title=21 CFR 172.822 – Sodium lauryl sulfate|work=gpo.gov|access-date=13 March 2016}} It is used as an emulsifying agent and whipping aid.{{cite book | author = Igoe, R. S. | date = 1983 | title = Dictionary of food ingredients | location = New York | publisher = Van Nostrand Reinhold Co.}}{{page needed|date=March 2016}} As an emulsifier in or with egg whites the United States Code of Federal Regulations require that it must not exceed 1,000 parts per million (0.1%) in egg white solids or 125 parts per million (0.0125%) in frozen or liquid egg whites and as a whipping agent for the preparation of marshmallows it must not exceed 0.5% of the weight of gelatine.{{cite web|url=https://www.ecfr.gov/cgi-bin/text-idx?SID=0ca7f8a00fa31be81df5a4560692d7cd&mc=true&node=se21.3.172_1822&rgn=div8|title=21 CFR 172.822 – Sodium lauryl sulfate|access-date=19 August 2021}} SLS is reported to temporarily diminish perception of sweetness.{{cite book | author = Adams, Michael J. | year = 1985 | title = Characterization and Measurement of Flavor Compounds | volume = 289 | chapter = Substances That Modify the Perception of Sweetness (Ch. 2) | pages = [https://archive.org/details/characterization0000unse/page/11 11–25] | doi = 10.1021/bk-1985-0289.ch002 | series = ACS Symposium Series | editor = Bills, Donald D. | editor2 = Mussinan, Cynthia J. | isbn = 9780841209442 | chapter-url = https://archive.org/details/characterization0000unse/page/11 }}

SDS is used in cleaning procedures,{{cite web|url=https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+1315|title=Sodium Lauryl Sulfate – National Library of Medicine HSDB Database|website=toxnet.nlm.nih.gov|access-date=2017-02-16}} and is commonly used as a component for lysing cells during RNA extraction or DNA extraction, inhibiting the activity of nucleases, enzymes that can degrade DNA, protecting the integrity of the isolated genetic material, and for denaturing proteins in preparation for electrophoresis in the SDS-PAGE technique.The acronym expands to "sodium dodecyl sulfate-polyacrylamide gel electrophoresis."

File:Protein-SDS interaction.png

In the case of SDS-PAGE, the compound works by disrupting non-covalent bonds in the proteins, and so denaturing them, i.e. causing the protein molecules to lose their native conformations and shapes. By binding to proteins at a ratio of one SDS molecule per 2 amino acid residues, the negatively charged detergent provides all proteins with a similar net negative charge and therefore a similar charge-to-mass ratio.{{cite book|last1=Janson|first1=Lee W.|first2=Marc|last2=Tischler|url=https://www.worldcat.org/oclc/794620168|title=The big picture: medical biochemistry|date=2012|publisher=McGraw-Hill|others=Tischler, Marc E.|isbn=978-0-07-163792-3|location=New York|oclc=794620168}} In this way, the difference in mobility of the polypeptide chains in the gel can be attributed solely to their length as opposed to both their native charge and shape.{{cite book|title=Fundamental Laboratory Approaches for Biochemistry and Biotechnology|last1=Ninfa|first1=Alexander|last2=Ballou|first2=David|last3=Benore|first3=Marilee|publisher=Wiley, John and Sons, Incorporated|year=2009|isbn=978-0470087664|location=United States|page=165}} This separation based on the size of the polypeptide chain simplifies the analysis of protein molecules.{{cite book|title=Fundamental Laboratory Approaches for Biochemistry and Biotechnology|last1=Ninfa|first1=Alexander|last2=Ballou|first2=David|publisher=John Wiley & Sons|year=1998|isbn=978-1-891-78600-6|location=Hoboken, New Jersey|page=129}}

Sodium lauryl sulfate is a widely used in the pharmaceutical field as an ionic solubilizer and emulsifier that is suitable for applications in liquid dispersions, solutions, emulsions and micro emulsions, tablets, foams and semi-solids such as creams, lotions and gels.{{cite web|title=Pharmaceuticals|url=https://pharmaceutical.basf.com/global/en.html|access-date=2021-04-27|website=pharmaceutical.basf.com|language=en}} Additionally, SLS aids in tablet wettability, as well as lubrication during manufacturing. Brand names of pharma-grade SLS include Kolliphor SLS and Kolliphor SLS Fine.{{cite web|title=Kolliphor® SLS|url=https://pharmaceutical.basf.com/global/en/drug-formulation/products/kolliphor-sls.html|access-date=2021-04-27|website=pharmaceutical.basf.com|language=en}}

SLS is used in an improved technique for preparing brain tissues for study by optical microscopy. The technique, which has been branded as CLARITY, was the work of Karl Deisseroth and coworkers at Stanford University, and involves infusion of the organ with an acrylamide solution to bind the macromolecules of the organ (proteins, nucleic acids, etc.), followed by thermal polymerization to form a "brain–hydrogel" (a mesh interspersed throughout the tissue to fix the macromolecules and other structures in space), and then by lipid removal using SDS to eliminate light scattering with minimal protein loss, rendering the tissue quasi-transparent.{{cite journal | last=Shen | first = Helen | year = 2013 | title=See-through brains clarify connections | journal = Nature | volume = 496 | issue = 7444; April 10 | page = 151 | doi = 10.1038/496151a | pmid = 23579658 | bibcode = 2013Natur.496..151S | doi-access = free }}{{better source|date=March 2016}}{{cite journal |author = Chung, K. |author2=Wallace, J. |author3=Kim, S.-Y. |author4=Kalyanasundaram, S. |author5=Andalman, A.S. |author6=Davidson, T.J. |author7=Mirzabekov, J.J. |author8=Zalocusky, K.A. |author9= Mattis, J. |author10=Denisin, A.K. |author11=Pak, Sally |author12=Bernstein, H. |author13=Ramakrishnan, C. |author14=Grosenick, L. |author15=Gradinaru, V. |author16=Deisseroth, K. |display-authors=3 | year = 2013 | title= Structural and molecular interrogation of intact biological systems | journal = Nature | volume = 497 | issue = 7449; May 16 | pages = 332–37 | doi = 10.1038/nature12107 | quote = Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. | pmid=23575631 | pmc=4092167|bibcode=2013Natur.497..332C }}

Along with sodium dodecylbenzene sulfonate and Triton X-100, aqueous solutions of SDS are popular for dispersing or suspending nanotubes, such as carbon nanotubes.{{cite journal|last1=Islam|first1=M. F.| year = 2003 | title=High Weight Fraction Surfactant Solubilization of Single-Wall Carbon Nanotubes in Water|journal=Nano Letters|volume=3|issue=2|pages=269–73|doi=10.1021/nl025924u|bibcode=2003NanoL...3..269I}}

SLS has been proposed as a potentially effective topical microbicide, for intravaginal use, to inhibit and possibly prevent infection by various enveloped and non-enveloped viruses such as the herpes simplex viruses, HIV, and the Semliki Forest virus.{{cite journal | title=Sodium lauryl sulfate, a microbicide effective against enveloped and nonenveloped viruses |author1=Piret J. |author2=Désormeaux, A. |author3=Bergeron, M.G. | journal=Curr. Drug Targets | year=2002 | volume = 3 | issue = 1 | pages = 17–30 | pmid=11899262 | doi=10.2174/1389450023348037 }}{{cite journal|title=In vitro and in vivo evaluations of sodium lauryl sulfate and dextran sulfate as microbicides against herpes simplex and human immunodeficiency viruses |author1=Piret J. |author2=Lamontagne, J. |author3=Bestman-Smith, J. |author4=Roy, S. |author5=Gourde, P. |author6=Désormeaux, A. |author7=Omar, R.F. |author8=Juhász, J. |author9=Bergeron, M.G. | journal = J. Clin. Microbiol. | year=2000 |volume = 38 | issue = 1 | pages = 110–19 |doi=10.1128/JCM.38.1.110-119.2000 | pmid=10618073 | pmc=86033 }}

Liquid membranes formed from SDS in water have been demonstrated to work as unusual particle separators.{{cite journal|journal=Science Advances|volume=4|author=Birgitt Boschitsch Stogin |display-authors=etal |title=Free-standing liquid membranes as unusual particle separators|issue=8|pages=eaat3276|date=August 24, 2018|doi=10.1126/sciadv.aat3276|pmid=30151426|pmc=6108570|bibcode=2018SciA....4.3276S}} The device acts as a reverse filter, allowing large particles to pass while capturing smaller particles.

Dodecyl alcohol is sulfated using sulfur trioxide. The reaction proceeds by initial formation of the pyrosulfate:

:{{chem2|2 SO3 + ROH → ROSO2\sO\sSO3H}}

:{{chem2|ROSO2\sO\sSO3H -> ROSO3H + SO3}}

Several million tons are produced annually.{{cite book|doi=10.1002/14356007.a25_747.pub2 |chapter=Surfactants |title=Ullmann's Encyclopedia of Industrial Chemistry |date=2019 |last1=Holmberg |first1=Krister |pages=1–56 |isbn=978-3-527-30673-2 }}

SDS can also be synthesized by treating lauryl alcohol with chlorosulfuric acid.{{cite journal |last1=Takei |first1=Kensuke |last2=Tsuto |first2=Keiichi |last3=Miyamoto |first3=Shigeyuki |last4=Wakatsuki |first4=Junya |title=Anionic surfactants: lauric products |journal=Journal of the American Oil Chemists' Society |date=February 1985 |volume=62 |issue=2 |pages=341–347 |doi=10.1007/BF02541402|s2cid=84286689 }}

The resulting half ester of sulfuric acid is then neutralized with alkali.

Lauryl alcohol can be used in pure form or as a mixtures of fatty alcohols. When produced from these sources, "SDS" products are a mixture of various sodium alkyl sulfates with SDS being the main component.{{cite book | author = Gloxhuber, C., & Kunster, K. | title = Anionic Surfactants: Biochemistry, toxicology, dermatology | edition = 2nd | location = New York | date = 1992}}{{page needed|date=March 2016}} For instance, SDS is a component, along with other chain-length amphiphiles, when produced from coconut oil, and is known as sodium coco sulfate (SCS).{{cite patent | title = Process of making solid foams from polymer emulsions | country = US | number = 3,491,033 | pubdate = 1970 | url=https://www.google.com/patents/US3491033}} SDS is available commercially in powder, pellet, and other forms (each differing in rates of dissolution), as well as in aqueous solutions of varying concentrations.{{citation needed|date=March 2016}}

SDS is not carcinogenic in low concentrations according to some{{clarify|date=August 2023}} studies.{{cite journal |author=Cosmetic Ingredient Review (CIR) program Expert Panel |title=Final Report on the Safety Assessment of Sodium Lauryl Sulfate and Ammonium Lauryl Sulfate |journal=Int. J. Toxicol. | year=1983 | volume=2 | issue=7 | pages=127–81 | doi = 10.3109/10915818309142005 |s2cid=34123578 | url = http://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/pr216.pdf | access-date = 13 March 2016 | quote = [Quoting:] Carcinogenesis. A one-year chronic oral study using beagles showed that Sodium Lauryl Sulfate at concentrations up to 2% in the diet was not tumorigenic or carcinogenic. [p. 157] / Summary… In mutagenesis studies, rats fed 1.13% and 0.56% Sodium Lauryl Sulfate in the diet for 90 days produced no more chromosomal aberrations or clastogenic effects than did a control diet. [p. 175]. / Conclusion. Sodium Lauryl Sulfate and Ammonium Lauryl Sulfate appear to be safe in formulations designed for discontinuous, brief use followed by thorough rinsing from the surface of the skin. In products intended for prolonged contact with skin, concentrations should not exceed 1%. [p. 176.] }}.{{cite journal |author=Wilma F. Bergfeld, Chair, and the Cosmetic Ingredient Review (CIR) program Expert Panel |title=Final report on the safety assessment of sodium lauryl sulfate and ammonium lauryl sulfate |journal=Int. J. Toxicol. |year=2005 |volume=24 | issue=1 | pages=1–102, esp. 89–98 | url = http://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PRN475.pdf | access-date = 13 March 2016 | quote = [Quoting:] Sodium Lauryl Sulfate and Ammonium Lauryl Sulfate appear to be safe in formulations designed for discontinuous, brief use followed by thorough rinsing from the surface of the skin. In products intended for prolonged contact with skin, concentrations should not exceed 1%… New studies confirmed the irritant properties of these ingredients and reinforced the concentration limit of 1% or leave-on uses established by the [earlier] Panel. [p. 89] / The available studies that looked for carcinogenesis failed to find evidence that Ammonium Lauryl Sulfate are [sic.] carcinogenic. None of the available data suggested that SLS or Ammonium Lauryl Sulfate could be carcinogenic. Despite assertions to the contrary on the Internet, the carcinogenicity of these ingredients is only a rumor. [pp. 89ff] }}. Like all detergents, sodium lauryl sulfate removes oils from the skin, and can cause skin and eye irritation.{{citation needed|date=March 2016}} It has been shown to irritate the skin of the face, with prolonged and constant exposure (more than an hour) in young adults.{{cite journal |vauthors=Marrakchi S, Maibach HI | year = 2006 | title=Sodium lauryl sulfate-induced irritation in the human face: regional and age-related differences |journal=Skin Pharmacol Physiol |volume=19 |issue=3 |pages=177–80 | pmid=16679819 |doi=10.1159/000093112 | s2cid = 35890797 }} SDS may worsen skin problems in individuals with chronic skin hypersensitivity, with some people being affected more than others.{{cite journal |author=Agner T |title=Susceptibility of atopic dermatitis patients to irritant dermatitis caused by sodium lauryl sulphate |journal=Acta Derm. Venereol. |volume=71 |issue=4 |pages=296–300 |year=1991 |doi=10.2340/0001555571296300 |pmid=1681644 |s2cid=37806228 |doi-access=free }}{{cite journal |vauthors=Nassif A, Chan SC, Storrs FJ, Hanifin JM |title=Abnormal skin irritancy in atopic dermatitis and in atopy without dermatitis |journal=Arch Dermatol |volume=130 |issue=11 |pages=1402–07 |date=November 1994 |pmid=7979441 |doi= 10.1001/archderm.130.11.1402}}{{cite journal |vauthors=Löffler H, Effendy I |title=Skin susceptibility of atopic individuals |journal=Contact Derm. |volume=40 |issue=5 |pages=239–42 |date=May 1999 |pmid=10344477 |doi= 10.1111/j.1600-0536.1999.tb06056.x|s2cid=10409476 }}

SDS is a common ingredient in toothpastes due to its low cost,{{cite book | author = Lippert, Frank | year = 2013 | title = Toothpastes | volume = 23 | series = Monographs in Oral Science | others = Series Eds.: Huysmans, M.C., Lussi, A. & Weber, H.-P. | chapter = An Introduction to Toothpaste—Its Purpose, History and Ingredients | editor = van Loveren, Cor | pages = 1–14, esp. 12 | location = Basel, CHE | publisher = Karger | doi = 10.1159/000350456 | pmid = 23817056 | isbn = 978-3-318-02206-3 }} its lack of impact on taste, and its desirable action as a foaming agent.

SDS may reduce the amount of bad breath-causing volatile sulfur compounds (VSCs) in the mouth.{{cite book |author1=Dadamio, J. |author2=Laleman, I. |author3=Quirynen, M. | year = 2013 | title = Toothpastes |volume=23 | series = Monographs in Oral Science | others = Series Eds.: Huysmans, M.C., Lussi, A. & Weber, H.-P. | chapter = The Role of Toothpastes in Oral Malodor Management | editor = van Loveren, C. | pages = 45–60, esp. 49–52 | location = Basel, CHE | publisher = Karger | doi = 10.1159/000350472 |pmid=23817059 |isbn=978-3-318-02206-3 }} A series of small crossover studies (25–34 patients) have supported the efficacy of SLS in the reduction of VSCs, and its related positive impact on breath malodor, although these studies have been generally noted to reflect technical challenges in the control of study design variables.

Primary sources from the group of Irma Rantanen at University of Turku, Finland claim that SLS-containing pastes cause more dry mouth (xerostomia) than their proposed alternative. However, a 2011 Cochrane review of these studies, and of the more general area, concludes that there "is no strong evidence... that any topical therapy is effective for relieving the symptom of dry mouth."See {{cite journal |author1=Furness S. |author2=Worthington, H.V. |author3=Bryan, G. |author4=Birchenough, S. |author5=McMillan R. |year=2011 |title=Interventions for the management of dry mouth: topical therapies |journal=Cochrane Database Syst Rev |volume=7 |issue=12; December |page=CD008934 |doi=10.1002/14651858.CD008934.pub2 |pmid=22161442 |quote=[Quoting abstract:] There is no strong evidence from this review that any topical therapy is effective for relieving the symptom of dry mouth.}} See Rantanen, et al. (2003) J. Contemp. Dent. Pract. 4(2):11–23, [https://www.ncbi.nlm.nih.gov/pubmed/12761586], and Rantanen, et al. (2003) Swed. Dent. J. 27(1):31–34, [https://www.ncbi.nlm.nih.gov/pubmed/12704946], referenced therein.

A safety concern has been raised on the basis of several studies regarding the effect of toothpaste SDS on aphthous ulcers (more specifically, mouth ulcers or "canker sores"), commonly referred to as canker or white sores. According to the NHS and Alessandro Villa of the Miami Cancer Institute, SLS is a cause for concern for mouth ulcers.{{cite web | last=Amenabar | first=Teddy | title=Got canker sores? Try switching your toothpaste. | website=The Washington Post | date=2024-10-09 | url=https://www.washingtonpost.com/wellness/2024/10/09/canker-sore-toothpaste-sls/ | access-date=2025-04-11}}{{cite web|url=https://www.nhs.uk/conditions/mouth-ulcers/|title=Mouth ulcers|date=18 October 2017 |quote=do not use toothpaste containing sodium lauryl sulphate|publisher=NHS}}Some of the published studies, from latest to earliest, are as follows. (i) A 2012 double-blind crossover study of 90-patients failed to find a significant difference in number of ulcers between groups using SLS-containing toothpaste, versus a group using an SLS-free toothpaste, but did suggest significant reduction in ulcer duration and improvement in patient pain scores, see {{cite journal | last1 = Shim | first1 = Y. J. | last2 = Choi | first2 = J. -H. | last3 = Ahn | first3 = H. -J. | last4 = Kwon | first4 = J. -S. | title = Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: A randomized controlled clinical trial | doi = 10.1111/j.1601-0825.2012.01920.x | journal = Oral Diseases | pages = 655–60 | year = 2012 | pmid = 22435470 | volume=18| issue = 7 }}, a study also cited in the Lippert (2013) book chapter. (ii) A 1999 double-blind crossover study of 47 patients failed to find any statistically significant difference in the number, episodes, and duration of such ulcers between these two groups, and of pain scores between them, see {{cite journal|journal=Oral Dis. |date=January 1999 |volume=5 |issue=1 |pages=39–43|title=The effect of a sodium lauryl sulfate-free dentifrice on patients with recurrent oral ulceration|vauthors=Healy CM, Paterson M, Joyston-Bechal S, Williams DM, Thornhill MH |pmid=10218040 |doi=10.1111/j.1601-0825.1999.tb00062.x}} (iii) A 1997 study suggested a significantly higher number of ulcers after SLS toothpaste use, versus its control group, see {{cite journal |vauthors=Chahine L, Sempson N, Wagoner C |title=The effect of sodium lauryl sulfate on recurrent aphthous ulcers: a clinical study |journal=Compend. Contin. Educ. Dent. |volume=18 |issue=12 |pages=1238–40 |date=December 1997 |pmid=9656847 }}, a study also cited in the Lippert (2013) book chapter. (iv) A 1996 follow-up 30-patient double-blind crossover study and a 1994 preliminary 10-patient crossover study by the same authors suggested significantly higher numbers of aphthous ulcers after using SLS-containing toothpaste, compared with an SLS-free toothpaste, see {{cite journal |vauthors=Herlofson BB, Barkvoll P |title=The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers |journal=Acta Odontol. Scand. |volume=54 |issue=3 |pages=150–53 |date=June 1996 |pmid=8811135 |doi= 10.3109/00016359609003515}} and {{cite journal |vauthors=Herlofson BB, Barkvoll P |title=Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study |journal=Acta Odontol. Scand. |volume=52 |issue=5 |pages=257–59 |date=October 1994 |pmid=7825393 |doi= 10.3109/00016359409029036}} As Lippert notes, of 2013, "very few... marketed toothpastes contain a surfactant other than SLS [SDS]," and leading manufacturers continue to formulate their produce with SDS. According to Allesandro Villa of the Miami Cancer Institute, one theory is that SLS disrupts the protective layer of mucus covering the mouth.

• Sodium tetradecyl sulfate, another anionic surfactant in common use
• Mouth ulcer

{{Reflist}}

• [https://health.howstuffworks.com/mental-health/human-nature/perception/orange-juice-toothpaste.htm Josh Clark, "Why does orange juice taste bad after you brush your teeth?"]
• {{YouTube|id=Rod7nmKSWF0|title=This improbable membrane can trap flies in a jar—and odor in a toilet}} published on Aug 24, 2018 Science (journal)

{{Laxatives}}

Category:Organic sodium salts

Category:Cleaning product components

Category:Anionic surfactants

Category:Laxatives

Category:Excipients

Category:Reagents for biochemistry

Category:Sulfate esters

Category:Dodecyl compounds